A5036370298- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Craniofacial Disorders and Treatments
- Virology and Viral Diseases
- Celiac Disease Research and Management
- S100 Proteins and Annexins
- interferon and immune responses
- Viral Infections and Immunology Research
- Calcium signaling and nucleotide metabolism
- RNA and protein synthesis mechanisms
- Immune Response and Inflammation
- Mosquito-borne diseases and control
- Hedgehog Signaling Pathway Studies
- RNA regulation and disease
- Neonatal Health and Biochemistry
- Cleft Lip and Palate Research
- Chromosomal and Genetic Variations
- Transgenic Plants and Applications
- SARS-CoV-2 and COVID-19 Research
- Telemedicine and Telehealth Implementation
University of Pittsburgh
2011-2024
Children's Hospital of Pittsburgh
2011-2024
University of Pittsburgh Medical Center
2021-2023
Tongji University
2017
Albert Einstein College of Medicine
2007-2013
Purdue University West Lafayette
1999-2010
State Street (United States)
2003
Lehigh University
2002
Birmingham City Hospital
1990
ABSTRACT The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving membrane with that cell. These are triggered low pH, their structures strikingly similar in both prefusion dimer postfusion homotrimer conformations. Here we have compared cholesterol interactions during these two groups viruses. Using cholesterol-depleted insect cells, showed Semliki Forest (SFV) Sindbis were strongly promoted cholesterol, sterol dependence laboratory field isolates...
The enveloped alphaviruses include important and emerging human pathogens such as Chikungunya virus Eastern equine encephalitis virus. Alphaviruses enter cells by clathrin-mediated endocytosis, exit budding from the plasma membrane. While there has been considerable progress in defining structure function of viral proteins, relatively little is known about host factors involved alphavirus infection. We used a genome-wide siRNA screen to identify that promote or inhibit infection cells. Fuzzy...
The budding reactions of a number enveloped viruses use the cellular machinery involved in formation luminal vesicles endosomal multivesicular bodies (MVB). Budding these is dependent on presence specific late-domain motifs membrane-associated viral proteins. Such usually involve ubiquitin and are blocked by expression an ATPase-deficient form VPS4, AAA+ ATPase believed to be required late MVB pathway for disassembly/release machinery. Here we examined role late-domain-containing rhabdovirus...
Type III interferons are potent antiviral cytokines important for regulation of viruses that infect at mucosal surfaces. Studies using mice lacking the Ifnlr1 gene encoding type interferon receptor have demonstrated signaling through this is critical protection against influenza virus, norovirus, and reovirus. Using a genetic approach to disrupt murine cytokine genes Ifnl2 Ifnl3 , we found these fully recapitulate impaired control observed in . Our results support idea an exclusive role...
Significance Protein folding and oligomeric complex assembly are essential for protein homeostasis. These processes orchestrated by a network of host chaperones that interact with nascent formed polypeptides. We investigated the mechanism which ubiquitous, essential, molecular chaperone, TRiC, folds an aggregation-prone subunit viral capsid. Structural studies, mass spectrometry, in vitro experiments provided insights into cooperation cochaperone, prefoldin, assembles multimers. As...
Abstract Mammalian orthoreovirus (reovirus) infects most mammals and is associated with celiac disease in humans. In mice, reovirus the intestine disseminates systemically to cause serotype-specific patterns of brain. To identify receptors conferring serotype-dependent neuropathogenesis, we conducted a genome-wide CRISPRa screen identified paired immunoglobulin-like receptor B (PirB) as candidate. Ectopic expression PirB allowed binding infection. extracelluar D3D4 region required for...
ABSTRACT Several viruses induce intestinal epithelial cell death during enteric infection. However, it is unclear whether proapoptotic capacity promotes or inhibits replication in this tissue. We infected mice with two reovirus strains that infect the intestine but differ to alter immunological tolerance new food antigen. Infection strain T1L, which induces an inflammatory immune response fed antigen, prolonged intestine, whereas T3D-RV, does not response, rapidly cleared from intestine....
ABSTRACT Mice expressing the Fv-4 gene are resistant to infection by ecotropic murine leukemia viruses (MuLVs). The encodes an envelope (Env) protein whose putative receptor-binding domain resembles that of MuLV Env protein. Resistance MuLVs appears result from viral interference involving binding endogenously expressed env -encoded receptor, although immune system also plays a role in resistance. is processed normally and can be incorporated into virus particles but unable promote entry....
Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption ligand binding NgR1 and subsequent signaling can improve neuron outgrowth, making an important therapeutic target for diverse neurological conditions such as spinal crush injuries Alzheimer’s disease. Human serves mammalian orthoreovirus (reovirus), but mechanism virus–receptor engagement is unknown. To elucidate how mediates cell entry...
The role of glycoprotein membrane-spanning domains in the process membrane fusion is poorly understood. It has been demonstrated that replacing all or part domain a viral protein with sequences encode signals for glycosylphosphatidylinositol linkage attachment abrogates activity. suggested, however, actual amino acid sequence not critical activity proteins. We have examined function Moloney murine leukemia virus envelope proteins substitutions domain. Envelope bearing proline 617 are...
Cholesterol homeostasis is required for the replication of many viruses, including Ebola virus, hepatitis C and human immunodeficiency virus-1. Niemann-Pick C1 (NPC1) an endosomal-lysosomal membrane protein involved in cholesterol trafficking from late endosomes lysosomes to endoplasmic reticulum. We identified NPC1 CRISPR RNA interference screens as a putative host factor infection by mammalian orthoreovirus (reovirus). Following internalization via clathrin-mediated endocytosis, reovirus...
The function of the mammalian orthoreovirus (reovirus) σNS nonstructural protein is enigmatic. an RNA-binding that forms oligomers and enhances stability bound RNAs, but mechanisms by which it contributes to reovirus replication are unknown. To determine σNS-RNA binding in replication, we engineered mutants deficient capacity. We found alanine substitutions positively charged residues a predicted domain decrease RNA-dependent oligomerization. define steps facilitated property σNS,...
Celiac disease is an immune-mediated intestinal disorder that results from loss of oral tolerance (LOT) to dietary gluten. Reovirus elicits inflammatory Th1 cells and suppresses Treg responses antigen in a strain-dependent manner. Strain type 1 Lang (T1L) breaks tolerance, while strain 3 Dearing reassortant virus (T3D-RV) does not. We discovered infection by T1L mice leads the recruitment activation NK mesenteric lymph nodes (MLNs) I IFN-dependent Once activated following infection, produce...
Abstract The mammalian orthoreovirus (reovirus) σNS protein is required for formation of replication compartments that support viral genome and capsid assembly. Despite its functional importance, a mechanistic understanding lacking. We conducted structural biochemical analyses mutant forms dimers instead the higher-order oligomers formed by wildtype (WT) σNS. crystal structure shows interact with each other using N-terminal arms to form helical assembly resembling WT filaments in complex RNA...
Engagement of cell surface receptors by viruses is a critical determinant viral tropism and disease. The reovirus attachment protein σ1 binds sialylated glycans proteinaceous to mediate infection, but the specific requirements for different types are not entirely known. To identify host factors required reovirus-induced death, we conducted CRISPR-knockout screen targeting over 20,000 genes in murine microglial BV2 cells. Candidate cause death were highly enriched sialic acid synthesis...
Background: Toll-like receptor 4 (TLR4) has been implicated in inflammation-induced bone destruction various chronic diseases; however, its direct influence on healing is not well understood. The authors’ previous study showed accelerated with higher osteoclastogenesis gene expression toll-like knockout mice (TLR4 -/- ). This aimed to further elucidate the underlying cellular mechanisms during fracture by generating a myeloid cell-specific model (Lyz-TLR4 mice). Methods: Calvarial defects,...
Physical distancing imposed by the COVID-19 pandemic has led to alterations in routines and new responsibilities for much of research community. We provide some tips how teams can cope with physical distancing, which require a change we define productivity. Importantly, need maintain strengthen social connections this time when can’t be physically together.
Assembly of retrovirus particles is promoted by interaction the Gag polyprotein with RNA. Nonspecific RNA association nucleocapsid domain (NC) induces dimerization through protein−protein contacts in capsid (CA), followed higher order assembly to form immature virus particle. NMR relaxation studies were conducted investigate initial steps Rous sarcoma (RSV) examining nucleic acid a fragment comprising C-terminal CA (CTD) postulated mediate dimerization, spacer region between and NC (SP), NC....
Background: Inflammation is integral to the injury response. The inflammatory response essential host defense against infection and also tissue regeneration repair. Toll-like receptors (TLRs) are critical activators of innate immune present attractive therapeutic targets for inflammation-modulated regeneration. authors’ previous study showed that depletion TLR4 resulted in accelerated skull bone healing concurrent with increased expression osteoclastogenic genes. As such, study, authors used...
An audit of the work a lipid clinic revealed need to promote awareness problem hypercholesterolaemia, particularly among ethnic minority groups. Significant reductions in serum levels and blood pressure were achieved, though target reached only 40 per cent patients. Efforts encourage weight reduction obese discourage smoking had limited success. The establishment ensures ready access paramedical advice permits effective treatment hyperlipidaemia other coronary risk factors. Such service...
Mammalian orthoreovirus (reovirus) strains type 1 Lang (T1L) and 3 Dearing-RV (T3D-RV) infect the intestine in mice but differ induction of inflammatory responses. T1L infection is associated with blockade oral immunological tolerance to newly introduced dietary antigens, whereas T3D-RV not. leads an increase infiltrating phagocytes, including macrophages, gut-associated lymphoid tissues that are not observed infection. However, function macrophages reovirus intestinal unknown. Using cells...